Topic 8

• Mutagenic agents


  High energy and ionising radiation including α and β particles, x-ray, gamma rays, and ultraviolet light
• Carcinogens


  Chemicals that can alter the structure of DNA and interfere with transcription, including chemicals in tobacco smoke, mustard gas and peroxides
• Gene mutations


  1. Alteration of a base in the sequence of bases for one gene

  2. Likely to occur during DNA replication in the cell cycle

  3. Can be spontaneous but frequency increased by mutagenic agents

  
• Gene mutations


  Can result in a different amino acid sequence in the encoded polypeptide
• Different amino acid sequence

  Results in a different 3D shape and non-functioning protein
• Alterations to the genes can result in a mutation that causes cancer
• Types of gene mutations

  • Addition
  • Deletion
  • Substitution
  • Inversion
  • Duplication
  • Translocation of bases
• Addition


  One extra base being added to the sequence, causing a frameshift and potentially very different amino acid sequence
• Deletion


  One base is deleted from the sequence, causing a frameshift to the left and potentially a non-functioning protein
• Substitution


  One base has been changed for a different base, but no frameshift, so may still code for the same amino acid
• Duplication


  One particular base is duplicated at least once in the sequence, causing a frameshift to the right and a different amino acid sequence
• Translocation of bases


  A section of bases on one chromosome detaches and attaches to a different chromosome, causing significant impacts on gene expression and phenotype
• Inversion


  A section of bases detach from the DNA sequence and re-join inverted, resulting in different amino acids being coded for in this region

  
• Cancer can result from mutations in genes that regulate mitosis, leading to uncontrollable cell division and tumour formation
• Benign tumour


  Grows slowly, produces adhesive molecules to stick cells together, often encapsulated, can be removed with low chance of recurrence

  
• Malignant tumour


  Grows rapidly, cell nucleus becomes large and unspecialised, does not produce adhesive molecules, metastasises and grows projections into surrounding tissues, develops own blood supply
• Causes of tumour development

  • Mutation in tumour suppressor gene and/or oncogene
  • Abnormal methylation of tumour suppressor genes and oncogenes
  • Increased oestrogen concentrations
• Oncogenes


  Mutated version of a proto-oncogene that permanently activates cell division

  
• Tumour suppressor genes


  Produce proteins to slow down cell division and cause cell death if DNA copying errors are detected

  
• Hypermethylation of tumour suppressor genes

  Inactivates the gene, allowing cell division to continue
• Hypomethylation of oncogenes


  Permanently switches the gene on, resulting in uncontrolled cancer cell division

  
• Increased oestrogen concentrations


  Can activate proto-oncogenes, leading to permanent cell division and tumour growth

  
• Gene mutations can occur in DNA replication and the rate can be increased by mutagenic agents

  
• Tumours can be benign or malignant
• Tumours can develop due to mutations and abnormal methylation of tumour suppressor genes and oncogenes, as well as increased oestrogen concentrations
• Links to other topics

  • Gene mutations link to genetic diversity in topic 4
  • Gene mutations link to DNA structure and the genetic code
  • Gene mutations link to protein structure
  • Cancer and tumour development link to the cell cycle and mitosis

  
• Essay links


  • Gene mutations
  • Genetic diversity
  • DNA structure and the genetic code
  • Protein structure
  • Cell cycle and mitosis

  
• Totipotent stem cells


  Can divide to produce any type of body cell, found only in early mammalian embryos

  
• Pluripotent stem cells


  Found in embryos, can become almost any type of cell, used in research with prospect of treating human disorders

  
• Multipotent and unipotent stem cells


  Found in mature mammals, can divide to form a limited number of different cell types
• Induced pluripotent stem cells (iPS cells)


  Created from adult unipotent cells by switching on genes that were previously switched off, similar to embryonic pluripotent stem cells but without destroying an embryo

  
• Transcription factors


  Proteins that bind to DNA in the nucleus and initiate transcription of genes, enabling cell specialisation
• Oestrogen


  Can initiate transcription by binding to receptors and activating genes, including proto-oncogenes, leading to uncontrolled cell division

  
• Transcription factor


  Protein that binds to DNA in the nucleus and initiates transcription of genes
• Transcription


  1. Transcription factor binds to DNA

  2. Transcription begins

  3. mRNA molecule created

  4. mRNA translated in cytoplasm to create protein

  
• Without the binding of a transcription factor, the gene is inactive, and the protein won't be made
• Transcriptional factors in eukaryotes

  Can stimulate or inhibit transcription of target genes by moving from cytoplasm into nucleus